A major goal of opioid abuse research is to identify the various biological, pharmacological and situational factors that contribute to opioid abuse. One important component of this research involves examining differences in opioid sensitivity across subject populations. This research has shown that sensitivity to the effects of opioids often differs across age groups. Although the mechanisms responsible for these differences are not fully understood, there are data indicating that age-related alterations in opioid receptor physiology may play a role. Such alterations may influence an individual's response to opioids, and may result in large differences in opioid sensitivity across subject populations. The purpose of this research project is to examine age-related differences in sensitivity to the antinociceptive (i.e., analgesic) effects of mu opioids in the warm-water, tail-withdrawal procedure. In this procedure, rats are restrained and the latencies to remove their tails from 50 and 55 C water are recorded. In experiment I, the antinociceptive effects of several mu opioids will be examined in young (3 months), mature, (12 months) and aged (24 months) rats. The aim of this experiment is to quantify age- related differences in sensitivity to the antinociceptive effects of mu opioids, and to determine if these differences are influenced by the intensity of the nociceptive stimulus (i.e., water temperature) and/or the intrinsic efficacy of the test drug (i.e., its ability to initiate a cellular response after binding to its receptor site). In experiment II, the development of tolerance and cross-tolerance to the effects of mu opioids will be examined across the three age groups. In the tail-withdrawal procedure, the antinociceptive effects of several mu opioids will be examined before and during a regimen of chronic morphine administration (20 mg/kg b.i.d.). The aim of this experiment is to quantify age-related differences in the speed and magnitude to which tolerance develops to the effects of mu opioids, and to determine if these differences are influenced by an opioid's intrinsic efficacy.